ABSTRACT Although the respiratory acclimatization to chronic hypoxia has been well described, specific information as to the nature of the cardiovascular component of the acclimatization response is lacking and a convenient animal model has been unavailable. We propose to expose chronically instrumented sheep to chronic hypoxia in an environmental chamber for 4-5 days to test the hypothesis that neurohumoral adjustments, probably initiated by arterial chemoreflexes, provide a redistribution of systemic flow which sustains a pattern of 02 conservation. We will measure regional blood flow distribution in chronic hypoxia to skeletal muscle, GI tract, kidney (cortex), respiratory muscles, brain, and heart by serial injections of radiolabelled microspheres (5 isotopes) using the reference sample technique in the awake sheep. Subsequently, the role of the chemoreflexes in sustaining the regional circulatory adjustments during chronic hypoxia will be determined in sheep after chronic chemoreceptor denervation. Also, reversible vagal cold block will be used to assess the contribution of vagal cardiopulmonary afferents to the control of interorgan flow distribution in chronic hypoxia. Lastly, the contribution of autonomic efferent activity to the regulation of regional flow will be assessed by administration of selective adrenergic and cholinergic blocking agents. Ventilatory sensitivity to periodic C02 breathing will be used to determine the phase of acclimatization and to analyze cardiovascular responses to C02 hypoxia interactions.